Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis in more than 90% of cases. A method of detecting HCC accurately in its early stages would greatly improve our ability to manage and treat the disease. The UCLA Center aims to develop an effective and affordable blood-based method for the early detection of liver cancer. Our team consists of translational and clinical researchers with multi-disciplinary expertise in the areas of early detection, biomarkers, cancer surveillance, imaging, and biorepositories. We will focus on circulating tumor DNA (ctDNA) in the blood. ctDNA carryies cancer-specific genetic and epigenetic aberrations, which enable a noninvasive `liquid biopsy' for cancer diagnosis. Our diagnostic test is based on the DNA methylation patterns of cfDNA. Our integrated computational and experimental technologies can significantly boost the diagnostic power while dramatically reducing the cost. We have the following aims: (1) We will establish a longitudinal cohort of cirrhotic patients. The cirrhotic patients will be subject to ultrasound imaging screening and blood sample collection every 6 months. The UCLA liver clinic sees ~1200 cirrhotic patients per year. (2) We will establish a state-of-the-art biospecimen repository that includes plasma from individuals in the cohort, tissue from liver tumors after resection, and cirrhotic lesions after liver transplantation. (3) We will perform Phase 2 clinical assay validation and Phase 3 early detection validation for the diagnostic test. (4) We will contribute to the collaborative trans-network activities.